Sodium hydride → Jnj-54175446

HRID 2177654Notes

Reaction equation

HRID 2177654 reaction equation
CC1C=CC(S(O[CH2:12][CH2:13][C:14]2[N:18]([C:19]3[N:24]=[CH:23][C:22]([F:25])=[CH:21][N:20]=3)[N:17]=[N:16][C:15]=2[C@H:26]([NH:28][C:29](=[O:41])[C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[C:31]=2[Cl:40])[CH3:27])(=O)=O)=CC=1.[H-].[Na+]>C1COCC1>[Cl:40][C:31]1[C:32]([C:36]([F:39])([F:37])[F:38])=[CH:33][CH:34]=[CH:35][C:30]=1[C:29]([N:28]1[CH2:12][CH2:13][C:14]2[N:18]([C:19]3[N:20]=[CH:21][C:22]([F:25])=[CH:23][N:24]=3)[N:17]=[N:16][C:15]=2[C@H:26]1[CH3:27])=[O:41]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 90409707(R)-2-(4-(1-(2-chloro-3-(trifluoromethyl)benzamido)ethyl)-1-(5-fluoropyrimidin-2-yl)-1H-1,2,3-triazol-5-yl)ethyl 4-methylbenzenesulfonate

Product 1

HCID 90409366Jnj-54175446Yield 72.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To the solution of Intermediate 244 (12.9 g, 21.04 mmol, 1.0 equiv.) in THF (150 mL) was added NaH (60 wt % in mineral oil, 4.5 g, 112.38 mmol, 5.3 equiv.). The reaction solution was heated to 60° C. for 3 hours and then cooled to room temperature. The reaction was quenched with cold H2O and EtOAc. The organic layer was separated, dried over Na2SO4 and concentrated. The crude product was purified by column chromatography to afford Example 344: (R)-(2-chloro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyrimidin-2-yl)-4-methyl-6,7-dihydro-1H-[1,2,3]triazolo[4,5-c]pyridin-5(4H)-yl)methanone (6.70 g, 15.20 mmol, 72% yield) as a white solid. MS-ESI (m/z): [M+H]+ calcd for C18H13ClF4N6O, 440.79. found, 440.90. CHN analysis calcd for C18H13ClF4N6O: 49.04% C, 2.98% H, 19.05 N. found, 48.93% C, 3.25% H, 19.02 N. Chiral HPLC analysis: Chiral Pak AD-H column, 0.4 mL/min, 80% EtOH 20% hexane, major isomer 12.56 min, minor isomer 11.28 min.

Workup

  1. temperaturecooled to room temperature
  2. customThe reaction was quenched with cold H2O and EtOAc
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography
  7. customto afford Example 344

Sources & evidence

ORD record
ord-fc5b642e3ddf4e17a53ca3333610a824
Source dataset
uspto-grants-2015_06
Patent number
US09066946B2

Reaction notes

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